Remarkably, granule cells (GCs) of the olfactory bulb are continuously born throughout life, providing an excellent neuronal model for the study of both developmental and adult neurogenesis of inhibitory neurons in the brain. As with GCs born during development, cells born in the adult olfactory bulb must establish functional connections with existing neuronal components, including the fibers of the noradrenergic system. This system plays an essential role in sensory information processing in the bulb. The aims outlined in this application seek to understand the physiological role and cellular mechanisms by which the noradrenergic system modulates GC function in the olfactory bulb. In the first two aims, we propose to investigate the cellular mechanisms and physiological role of the excitatory action of noradrenaline on GCs in the main and accessory olfactory bulb. In the last aim, we propose to determine the role of the noradrenergic system on adult neurogenesis of GCs in the context of olfactory mediated behaviors. PUBLIC HEALTH RELEVANCE: The discovery that new neurons are born in the adult brain, also known as adult neurogenesis, has opened a promising area of research because of its therapeutic potential for rebuilding new circuits in neurodegenerative diseases as well as in aging. Among the cells that exhibit adult neurogenesis are the inhibitory granule cells of the olfactory bulb. These neurons are continuously born throughout life, providing an excellent neuronal model for the study of both developmental and adult neurogenesis. Throughout life, newly born granule cells perform the remarkable task of survival and proper integration into their new environment. As with granule cells born during development, the cells born in the adult must establish functional connections with existing neuronal components of the bulb. Among these components are the fibers of the noradrenergic system, an important neuromodulatory system in the bulb. Thus, the study of granule cell function in relation to the noradrenergic system also has medical implications. This system has extensive projections through the entire brain and plays an important role in neuronal excitability in physiological states such as attention, anxiety and emotions.